Synthesis of 5,6-benzo-1,2-diazabicyclo [2.2.2]octane

5,6-Benzo-1,2-diazabicyclo[2.2.2]octane was synthesized by nitrosation of 1,2,3,4-tetrahydrocinchoninic acid, reduction of the 1-nitroso derivative to 1-amino-1,2,3,4-tetrahydrocinchoninic acid, cyclodehydration of it to 3-oxo-5,6-benzo-1,2-diazabycyclo[2.2.2]octane, and reduction of the oxo group to a methylene group with lithium aluminum hydride.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1369–1371, October, 1970.     

1,4-diazabicyclo[2.2.2]octanes. I. Method for the synthesis of 1,4-diazabicyclo[2.2.2]octanes with functional substituents or condensed with benzene rings

The reaction of substituted 1,4-dimethylpiperazines and tetrahydroquinoxaline with dibromoethane gives the corresponding 1,4-diazabicyclo[2.2.2]octanes.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 272–275, February, 1976.     

Alkylated 1,4-diazabicyclo[2.2.2]octanes: self-association, catalytic properties, and biological activity

Aggregation of 1-hexadecyl-4-aza-1-azoniabicyclo[2.2.2]octane bromide in the presence of diethyl 4-nitrophenyl phosphate was studied using ¹H NMR spectroscopy. The quantitative characteristics of the aggregation were determined. The data obtained were used to explain the catalytic effect of micelles on the hydrolysis of the phosphate. It was found that the aggregation properties and biological activity of alkylated mono- and dicationic 1,4-diazabicyclo-[2.2.2]octanes are correlated.     

Synthesis of 1,4-diazabicyclo[2.2.2]octane

Double intramolecular cyclization of N,N-bis(2-chloroethyl)-N-N-bis(2-cyanoethyl)ethylenediamine leads to 1,4-bis(2-cyanoethyl)-1,4-diazoniabicyclo[2.2.2]octane dichloride, which undergoes decyanoethylation to 1,4-diazabicyclo[2.2.2]octane when it is heated. The structures of the compounds were confirmed by their IR and PMR spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 548–550, April, 1978.     

1,4-Diazabicyclo[2.2.2]octanes

1,4-Diazabicyclo[2.2.2]octane-2-carboxylic acid bis(methylbromide), which is readily converted with splitting out of hydrogen bromide to the corresponding quaternary betaine, was synthesized.     

Reduction of 2-oxa-3,7-diazabicyclo[3.3.0]octanes

The reduction of 2-oxa-6-oxo-3-phenyl-4-(R-phenyl)-7-(4-nitrophenyl)3,7-diazabicyclo[3.3.0]octanes with hydrazine hydrate in the presence of Raney nickel gave the corresponding amino alcohols. X-ray diffraction analysis established the stereochemistry of the molecule in the crystal of 1-(4-anilino)-3-[anilino(phenyl)methyl]-4-hydroxypyrrolidone-2.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 890–894, July, 1992.     

Synthesis of 1, 2-diazabicyclo [2.2.2] octane, 1, 2-diazabicyclo [3.2.1]-octane,and their derivatives

1, 2-Diazabicyclo [2.2.2] octane, its 6-methyl homolog, and 1, 2-diazabicyclo [3.2.1] octane are synthesized by a general method involving nitrosation of piperidine carboxylic acids, subsequent reduction to 1-aminopiperidine carboxylic acids, cyclization to 3-keto-1, 2-diazabicycloalkanes, reduction of the latter to 1, 2-diazabicycloalkanes. A number of 2-substituted 1, 2-diazabicyclo [2.2.2] octanes are synthesized.     

1, 4-Diazabicyclo [2.2.2] octanes

1,4-Diazabicyclo[2.2.2]octane hydrochloride methylchloride was obtained from N-benzoylpiperazine through 1-(2-hydroxyethyl)-4-benzoylpiperazine, 1-(2-acetoxyethyl)-4-benzoylpiperazine methyltosylate, 1-(2-hydroxyethyl)piperazine methylchloride, and 1-(2-chloroethyl)piperazine methylchloride.See [1] for communication I.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 845–847, June, 1976.     

The average structures of 2,3-diazabicyclo[2.2.1]hept-2-ene and 2,3-diazabicyclo[2.2.2]oct-2-ene

The average molecular structures of 2,3-diazabicyclo[2.2.1]hept-2-ene and 2,3-diazabicyclo[2.2.2] oct-2-ene have been determined by electron diffraction in the gas phase. The structural parameters were obtained by applying a least squares analysis on the molecular scattering intensity functions. For 2,3-diazabicyclo[2.2.1]hept-2-ene, C_s symmetry was assumed in calculating the geometry of the molecule. The parameters thus determined are: N₃=N₂ = 1.221 Å, N₃- C₄ = 1.445 Å, C₄-C₅ = 1.538 Å, C-H_(ave.) = 1.112 Å, < C₁N₂N₃ = 116.3°, < N₃C₄C₅ = 105.2°, < C₁C₄C₅ = 71.5°, C₄-C₇ = 1.547 Å, C₅-C₆ = 1.530 Å, < C₁C₇C₄ = 108.0°. For 2,3-diazabicyclo[2.2.2]oct-2-ene, C_2vsymmetry was assumed. The geometrical parameters are: N₃ = N₂ = 1.243 Å, N₃-C₄ = 1.473 Å, C₄-C₅ = 1.550 Å, C₅-C₆ = 1.516 Å, C-H_(ave.) = 1.119 Å,< C₁N₂N₃ = 115.1°, < N₃C₄C₅ = 109.1°, < C₆C₁C₄ = 71.6°.     

1,4-Diazabicyclo[2.2.2]octanes (review)

The literature data and our own experimental data on the synthesis and physical and chemical properties of 1,4-diazabicyclo[2.2.2]octanes as compared with their 4-deaza analogs (quinuclidines) are correlated. Methods for the practical utilization of the diazabicyclic systems are examined.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 723–738, June, 1976.     

Synthesis and separation of stereoisomeric 2,4,6,8-tetrasubstituted 3,7-dithia-1,5-diazabicyclo[3.3.0]octanes

Heterocyclization of hydrazine with aldehydes R-CHO (R = Me, Et, Prⁿ, Buⁿ, n-C₅H₁₁, Ph, 4-MeOC₆H₄, 3-Py) and H₂S leads to stereoisomeric 2,4,6,8-tetrasubstituted 3,7-dithia-1,5-diazabicyclo[3.3.0]octanes, which were separated by column chromatography. The trans-transoid-trans-configuration of tetramethyl(-ethyl,-propyl)-3,7-dithia-1,5-diazabicyclo-[3.3.0]octanes was inferred from the X-ray diffraction and ¹H and ¹³C NMR spectroscopic data.     

Synthesis and stereochemical analysis of isomeric N-substituted 5- and 6-propanilido-2-azabicyclo[2.2.2]octanes

The synthesis and stereochemical analysis of N-methyl and N-phenethyl-substituted 5- and 6-propanilido derivatives of 2-azabicyclo[2.2.2]octane were investigated for potential evaluation as analgesics related to fentanyl. Stereochemical assignments for the eight isomers reported here were made on the basis of nmr studies employing europium chemical shift reagents and hydrogen bonding studies employing ir analysis of the anilino- and propanilido-derivatives.     

Synthesis of fluorinated 2,6-heptanediones and 2-oxa-6- azabicyclo[2.2.2]octanes from 1,4-dihydropyridines

Electrophilic fluorination of Hantzsch-type 1,4-dihydropyridines with Selectfluor^® led to the formation of new fluorinated 2,6-heptanediones - dialkyl 2,4-diacetyl-2,4-difluoro-3-phenylpentanedioates. Novel 2,6-heptanedione derivatives in reaction with hydrazine hydrate easily form 6-amino-4,7-difluoro-3-hydroxy-1,3-dimethyl-5-oxo-8-phenyl-2-oxa-6-azabicyclo[2.2.2]octanes instead of the corresponding diazepine derivatives. The obtained 2-оxa-6-azabicyclo[2,2,2]octanes are thermally stable at the temperatures below 50°С. At higher temperatures rearrangement of 2-oxa-6-azabicyclo[2,2,2]octanes offers new fluorine-containing pyrazolinone derivatives - alkyl esters of 2-fluoro-2-((4-fluoro-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-4-yl)(phenyl)methyl)-3-oxobutanoates.     

Synthesis of derivatives of 1,2-diazabicyclo[2,2,2]octane. III

Synthesis of a number of 2-dialkylaminoalkyl-1, 2-diazabicyclo[2, 2, 2]octanes has been carried out starting from 1, 2-diazabicyclo[2, 2,2]-octane and passing through its 2-chloroacyl and 2-dialkylaminoacyl derivatives. It has been shown by means of NMR spectra that the methiodide of 2-methyl-1,2-diazabicyclo[2,2,2]octane has the structure of 1,2-dimethyl-2-aza-1-azoniabicyclo[2,2,2]octane iodide.For part II, see [2].     

A general and efficient synthesis of 3,6-diazabicyclo[3.2.1]octanes

A convenient and efficient synthesis of N⁶-substituted 3,6-diazabicyclo[3.2.1]octanes (6a-c) has been achieved starting from suitably substituted lactams, which were converted to nitroenamines followed by reductive cyclization to afford 3,6-diazabicyclo[3.2.1]octane-2-ones in good yields. These bicyclic lactams were then reduced to the corresponding 3,6-diazabicyclo[3.2.1]octanes and converted to the required N³,N⁶-disubstituted 3,6-diazabicyclo[3.2.1]octanes (7a-h), which were screened for α₁-adrenoceptors antagonistic activities.     

Diazabicycloalkanes with nitrogen atoms at the nodal positions. 12. Stephens rearrangement in substituted 1,4-diazabicyclo[2.2.2]octanes

The ylides formed from phenacyl derivatives of substituted diazabicyclooctanes decompose to the initial base or give products of the Stephens rearrangement, leading to an expansion of the ring. The direction of the reaction is determined by the presence of C-substituents in the bicyclic fragment. C-Phenyl groups, which are capable of stabilizing the transition state, ensure the occurrence of the rearrangement reaction.For Communication 11, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 664–668, May, 1985.